Integrated microbiome-metabolomics analysis reveals the potential therapeutic mechanism of Zuo-Jin-Wan in ulcerative colitis

Cai, Ying; Li, Siju; Zhang, Xiaojun; Cao, Xianglin; Liu, Deliang; Zhu, Yehan; Ye, Simin; Xu, Zengmei; Liao, Qiongfeng; Hong, Yanjun; Xie, Zenghong

doi:10.1016/j.phymed.2021.153914

Cited by 14 publications

(9 citation statements)

References 41 publications

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“…Notably, Pae treatment significantly increased the abundance of Lactobacillus and Bacteroides. Specifically, Lactobacillus and Bacteroides are known to enhance intestinal barrier function by promoting the expression of intestinal epithelial cell TJ proteins, reducing apoptosis of epithelial cells and regulating the thickness of the intestinal mucus layer [ 55 , 56 , 57 ]. The latter reports support the possibility that Pae may reduce DSS-induced intestinal inflammation in UC mice by increasing the abundance of Lactobacillus and Bacteroides.…”

Section: Discussionmentioning

confidence: 99%

Paeonol Ameliorates Ulcerative Colitis in Mice by Modulating the Gut Microbiota and Metabolites

Zheng

Zhang

et al. 2022

Metabolites

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Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the gastrointestinal tract. Recent studies demonstrate that the phenolic tannin paeonol (Pae) attenuates UC in mouse models by downregulating inflammatory factors. However, its molecular mechanism for UC treatment has not been explored from the perspective of the gut microbiota and metabolomics. In this study, we investigated the effects of Pae on colonic inflammation, intestinal microbiota and fecal metabolites in 3% dextran sodium sulfate (DSS) induced BALB/c UC mice. Pae significantly improved the clinical index, relieved colonic damage, reduced cytokine levels, and restored the integrity of the intestinal epithelial barrier in UC mice. In addition, Pae increased the abundance of gut microbiota, partially reversed the disturbance of intestinal biota composition, including Lactobacillus and Bacteroides, and regulated metabolite levels, such as bile acid (BA) and short-chain fatty acid (SCFA). In conclusion, our study provides new insight on Pae remission of UC.

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Section: Discussionmentioning

confidence: 99%

Paeonol Ameliorates Ulcerative Colitis in Mice by Modulating the Gut Microbiota and Metabolites

Zheng

Zhang

et al. 2022

Metabolites

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“…The increase of phylum Firmicutes and the decrease of phylum Bacteroidetes resulted in an increased F/B ratio in UC patients [ 2 ]. However, the preclinical study reported decreased F/B ratio in DSS-induced acute colitis rats [ 30 ]. In this study, fecal samples were collected at multiple time points during the development of acute colitis, which allowed us to characterize the dynamics of the relative abundance of the two phyla.…”

Section: Discussionmentioning

confidence: 99%

“…There is an increasing number of applications of both microbial sequencing and metabolomics in investigations of compound formulas [14,22,[27][28][29]. A few studies have systematically investigated the dynamic microbiome and metabolome disturbance and their associations in UC receiving herb interventions [15,30,31]. These research efforts have facilitated the translation of the TCM syndromes and holistic actions of CMs into modern scientific data and brought our understanding of the mystery of the old tradition to unprecedented depths [19,28].…”

Section: Discussionmentioning

confidence: 99%

Understanding the tonifying and the detoxifying properties of Chinese medicines from their impacts on gut microbiota and host metabolism: a case study with four medicinal herbs in experimental colitis rat model

Gao

Yan

et al. 2022

Chin Med

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Background Chinese medicines (CMs) have emerged as an alternative therapy for ulcerative colitis through reinforcing the vital qi and/or eliminating the pathogenic factors according to the traditional Chinese medicinal theory. Presystemic interactions of CMs with gut microbiota and the associated metabolic network shift are believed to be essential to achieve their holistic health benefits in traditional oral application. Methods This study first employed 16S rDNA-based microbial profiling and mass spectrometry-based urinary metabolomics to simultaneously evaluate four single CMs frequently prescribed as main constituent herbs for alleviating UC, the tonic ginseng and Astragali Radix (AR) and the detoxifying Scutellaria Radix (SR) and Rhubarb, on a dextran sodium sulfate (DSS)-induced colitis rat model, with aims to understanding the tonifying or detoxifying properties of CMs through clinical phenotypes, the common features and herb-specific signatures in gut microbial alterations and the associated host metabolic shifts. Colitis was induced in rats receiving 5% DSS for consecutive 7 days. Control group received water alone. Herbal groups received 5% DSS and respective herbal preparation by gavage once daily. Body weight, stool consistency, and rectal bleeding were recorded daily. Feces and urine were freshly collected at multiple time points. On day 7, blood and colon tissues were collected to determine anti-/pro-inflammatory cytokines levels, colonic myeloperoxidase activity, and histopathologic alterations. Results Gut microbiome was more prone to herb intervention than metabolome and displayed increasing associations with metabolic dynamics. Although both the tonic and the detoxifying herbs alleviated colitis and caused some similar changes in DSS-induced microbiome and metabolome disturbance, the tonic herbs were more effective and shared more common microbial and metabolic signatures. The detoxifying herbs elicited herb-specific changes. Rhubarb uniquely affected phenylalanine metabolism and established high correlations between Akkermansia muciniphila and Parasutterella and hydroxyphenylacetylglycine and phenylbutyrylglycine, while SR caused significant elevation of steroidal glucuronides dehydropregnenolone glucuronide and estriol glucuronide, both displaying exclusive correlations with genus Acetatifactor. Conclusion Both tonic and detoxifying herbs tested ameliorated experimental colitis and elicited alternative microbial and host metabolic reprogramming. The findings highlight the importance of presystemic interactions with gut microbiota to host metabolic shifts and promote modern translation of tonic and detoxifying properties of CMs.

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“…The increase of phylum Firmicutes and the decrease of phylum Bacteroidetes resulted in an increased F/B ratio in UC patients [2]. However, the preclinical study reported decreased F/B ratio in DSS-induced active colitis rats [30]. In this study, fecal samples were collected at multiple time points during the development of acute colitis, which allowed us to characterize the dynamics of the relative abundance of the two phyla.…”

Section: Discussionmentioning

confidence: 99%

“…There is an increasing applications of both microbial sequencing and metabolomics in investigations of compound formulas [14,22,[27][28][29]. A few studies have systematically investigated the dynamic microbiome and metabolome disturbance and their associations in UC receiving herb interventions [15,30,31]. These research efforts have facilitated the translation of the TCM syndromes and holistic actions of CMs into modern scienti c data and brought our understanding of the mystery of the old tradition to unprecedented depths [19,28].…”

mentioning

confidence: 99%

Understanding the tonifying and the detoxifying properties of Chinese medicines from their impacts on gut microbiota and host metabolism: a case study with four medicinal herbs in experimental colitis rat model

Gao

Yan

et al. 2022

Preprint

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Background: Chinese medicines (CMs) have emerged as an alternative therapy for ulcerative colitis through reinforcing the vital qi and/or eliminating the pathogenic factors according to the traditional Chinese medicinal theory. Presystemic interactions of CMs with gut microbiota and the associated host metabolic network shift are believed to be essential to achieve their holistic health benefits in traditional oral application. Methods: This study first employed 16S rDNA-based microbial profiling and mass spectrometry-based urinary metabolomics to simultaneously evaluate single CMs frequently prescribed as main constituent herbs for alleviating UC, the tonic ginseng and Astragali Radix (AR) and the detoxifying Scutellaria Radix (SR) and Rhubarb, on a dextran sodium sulfate (DSS)-induced colitis rat model, with aims to understanding the tonifying or detoxifying properties of CMs through clinical phenotypes, the common features and herb-specific signatures in gut microbial alterations and the associated host metabolic shifts. Colitis was induced in rats receiving 5% DSS for consecutive 7 days. Control group received water alone. Herbal groups received 5% DSS and respective herbal preparation by gavage once daily. Body weight, stool consistency, and rectal bleeding were recorded daily. Feces and urine were freshly collected at multiple time points. On day 7, blood and colon tissues were collected to determine anti-/pro-inflammatory cytokines levels, colonic myeloperoxidase activity, and histopathologic alterations. Results: Gut microbiome was more prone to herb intervention than metabolome and displayed increasing associations with metabolic dynamics. Although both the tonic and the detoxifying herbs alleviated colitis and caused some similar changes in DSS-induced microbiome and metabolome disturbance, the tonic herbs were more effective and shared more common microbial and metabolic signatures. The detoxifying herbs elicited herb-specific changes. Rhubarb uniquely affected phenylalanine metabolism and established high correlations between Akkermansia muciniphila and Parasutterella and hydroxyphenylacetylglycine and phenylbutyrylglycine, while SR caused significant elevation of steroidal glucuronides dehydropregnenolone glucuronide and estriol glucuronide, both displaying exclusive correlations with genus Acetatifactor. Conclusions: Both tonic and detoxifying herbs tested ameliorated experimental colitis and elicited alternative microbial and host metabolic reprogramming. The findings highlight the importance of presystemic interactions with gut microbiota to host metabolic shifts and promote modern translation of tonifying and detoxifying properties of CMs.

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Integrated microbiome-metabolomics analysis reveals the potential therapeutic mechanism of Zuo-Jin-Wan in ulcerative colitis

Cited by 14 publications

References 41 publications

Paeonol Ameliorates Ulcerative Colitis in Mice by Modulating the Gut Microbiota and Metabolites

Paeonol Ameliorates Ulcerative Colitis in Mice by Modulating the Gut Microbiota and Metabolites

Understanding the tonifying and the detoxifying properties of Chinese medicines from their impacts on gut microbiota and host metabolism: a case study with four medicinal herbs in experimental colitis rat model

Understanding the tonifying and the detoxifying properties of Chinese medicines from their impacts on gut microbiota and host metabolism: a case study with four medicinal herbs in experimental colitis rat model

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